A-967. Lack of a Pharmacokinetic Effect Between Steady-State Tipranavir/Ritonavir (TPV/r) and Single-Dose Valacyclovir in Healthy Volunteers
Session: Poster Session: HIV Pharmacokinetics/Dynamics
Sunday, October 26, 2008: 12:00 AM
Room: Hall C
Background: Tipranavir (TPV) is a next generation protease inhibitor (PI) with potent activity against multiple PI-resistant HIV-1. This study determined the effects of steady-state TPV/r 500/200 mg bid on the pharmacokinetics (PK) of acyclovir, administered as the prodrug valacyclovir, a commonly used therapy for herpes virus infections. Methods: Open label, one-sequence cross-over PK study in HIV-negative adults administered single oral doses of valacyclovir 500 mg alone and in combination with TPV/r. Plasma drug concentrations were measured by validated LC/MS/MS; PK was determined by non-compartmental methods. The geometric mean ratio and 90% CI [GMR, 90% CI] was used to evaluate the drug interaction. Results: Twenty-six of 29 subjects completed the trial. With steady-state TPV/r, acyclovir Cmax decreased 4.9% [0.95, 0.88-1.02], Cp12h increased 18.9% [1.19, 1.11-1.27] and AUCinf increased 6.6% [1.07, 1.04-1.09]. The effect of single-dose valacyclovir on TPV Cmax, Cp12h and AUC12h were minimal (+2.3%, -1.9% and +1.0%, respectively) while RTV Cmax, Cp12h and AUC12h decreased 19.4%, 5.7% and 14.0%, respectively. Study medications were generally well tolerated. The majority of subjects experienced at least one AE, most of which were mild. As expected, the majority of AEs were gastrointestinal disorders. Three subjects discontinued TPV/r treatment as a result of drug-related increases in ALT/AST, including one subject who experienced mild upper abdominal pain. All subjects recovered without sequelae. Conclusions: When administered as a single dose of valacyclovir with steady-state TPV/r, there were no clinically important changes in acyclovir, TPV, or RTV PK. These results indicate that these drugs can be co-administered safely with no dose adjustments.
Daniel Haas, MD1, Herbert Eskoetter, MD1, John Sabo, MS2, Michael Kraft, MD3, Stefan Mauss, MD4, Xiuyu Cong, PhD5 and  J. P. Sabo,
Boehringer Ingelheim Pharmaceuticals, Inc. Role(s): Employee, Received: Salary., (1)Boehringer Ingelheim Corp., (2)Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, (3)Boehringer Ingelheim Spain, (4)Arzt für Innere Medizin, (5)Boehringer Ingelheim Pharmaceuticals, Inc.

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